Effect of steric and electronic properties of palladium complexes with bidentate diphosphine ligands on the basis of diphenyl oxide on arylation of amines

Article abstract of DOI:10.1007/s11176-005-0199-9

New complexes of palladium chloride with bidentate diphosphine ligands on the basis of 2,2′-bis(diorganylphosphino)diphenyl oxides were prepared by three methods, and their catalytic activity in arylation of amines was studied. 2005 Pleiades Publishing, Inc.

Full text of DOI:10.1007/s11176-005-0199-9

Russian Journal of General Chemistry, Vol. 75, No. 2, 2005, pp. 207 211. Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 2, 2005,
pp. 233 238.
Original Russian Text Copyright
2005 by Veits, Mutsenek.
Effect of Steric and Electronic Properties
of Palladium Complexes with Bidentate Diphosphine Ligands
on the Basis of Diphenyl Oxide on Arylation of Amines
Yu. A. Veits and E. V. Mutsenek
Lomonosov Moscow State University, Moscow, Russia
Received June 23, 2003
Abstract New complexes of palladium chloride with bidentate diphosphine ligands on the basis of 2,2 -
bis(diorganylphosphino)diphenyl oxides were prepared by three methods, and their catalytic activity in aryla-
tion of amines was studied.
Previously [1] we synthesized a series of bidentate
ligands on the basis of 2,2 -diphosphino-substituted
diphenyl oxide, differing from their analog with
phenyl substituents on phosphorus [2] in that their
phosphorus atom bore secondary and tertiary alkyl
radicals or their combinations. The interest in synthesis
of such compounds was provoked by the data of
Hamann and Hartwig [3], who showed in their study
on the cross coupling reaction of aniline with N,N-di-
methyl-4-bromoaniline that replacement of the di-
phenylphosphino groups in the catalyst, palladium(0)
2,2 -bis(diarylphosphino)diphenyloxide complex, by
di-o-tolylphosphino groups increases the conversion
from 30 to 80%. Comparison of the catalytic activities
of palladium complexes of our synthesized ligands
with variable steric and electron-donor characteristics
of the phosphorus atom may aid in assessment of the
role of key stages in cross coupling.
synthesized by stirring the reagents for 3 h at 60 C.
Ligands Ib and Ic with a more nucleophilic phos-
phorus atoms react with palladium chloride faster, but,
in view of the fact that complexes IIb and IIc are
thermally unstable and partially decompose at 60 C
already within 30 min, for their successful synthesis
reaction (1) should be accomplished at room tempera-
ture for 12 h.
The second synthetic approach to complexes II
(procedure b), that involves displacement by ligand I
of the more basic benzonitrile, seems more promising.
I + PdCl2(PhCN)2
IIb, IId + 2PhCN. (2)
Reaction (2) features high rate with various ligands,
mild conditions (THF, 20 C, several hours), high
yields, and facile product isolation. For comparison,
the yields of complex Id by the first and second
procedures are 25 and 95%, respectively.
The complexes of palladium chloride with ligands
(2-R1R2PC6H4)2O [Ia Ig, where R1 = R2 = Ph (Ia),
R1 = R2 = s-C6H11 (Ib); R1 = R2 = i-Pr (Ic), R1 =
R2 = t-Bu (Id), R1 = R2 = C6F5 (Ie); R1 = i-Pr, R2 =
t-Bu (If); R1 = t-Bu, R2 = Ph (Ig); were prepared by
three procedures. The first procedure (procedure a)
involves reaction of palladium chloride with an indi-
vidual ligand I in aqueous ethanol.
As ligands I are difficult to isolate pure in view of
their tendency for oxidation in solutions and partial
loss of products, we developed the third procedure for
preparing complexes II (procedure c), in which a
crude ligand I plays the role of substrate. To prepare
complexes II by this procedure, one cannot directly
use the reaction mixture containing ligand I and
palladium chloride, since tetramethylethylenediamine
is scarcely inferior to the phosphine ligands in com-
plex-forming ability and successfully competes with
them for place in the coordination sphere of palladium.
Therefore, for preparing crude ligands I certain mani-
pulations are required (see Experimental). After
removal of tetramethylethylenediamine in a vacuum
and addition of the complex of palladium chloride
with dibenzonitrile to the resulting oily ligands I,
complexes II can be prepared in 70 80% yields,
O
I + PdCl2
R1R2P
PR1R2
(1)
Pd
Cl
IIa IId
According to this procedure, complex IIa was
Cl
1070-3632/05/7502-0207 2005 Pleiades Publishing, Inc.

208
VEITS, MUTSENEK
Table 1. Results of cross coupling of 4-bromoacetophenone with amines IIIa IIIc in the presence of 0.5 mol% of
catalysts IIa IIg at 85 C [reaction (3)].
Yield of reaction products, % (GLC)
Comp. no.
R1
R2
IVa after 1 ha
IVb after 2 hb
IVc after 7 h
IIa
IIb
IIc
IId
IIe
IIf
Ph
Ph
47.4 (50.8)
79.0 (87.9)
(74.3)
76.3
54.9 (67.8)
79.4
45.2 (59.8)
57.7
58.9
70.5
56.0
31.5
60.7
92.2
85.9
cyclo-C6H11
i-Pr
t-Bu
C6F5
i-Pr
cyclo-C6H11
i-Pr
t-Bu
C6F5
t-Bu
Ph
(18.7)
37.6
IIg
t-Bu
71.2 (79.5)
51.0 (66.7)
a
b
Notes: Parenthesized are the yields after
2 and
6 h.
which is 20 25% higher than the yields by the first
and second procedures, because the isolable yields of
ligands I themselves are no higher than 55 70%. In
experimental conditions procedure c is similar to b,
which is not surprising, because they both are based
on the same reaction (2). The facility of product isola-
tion, high yields, high rates, and mild conditions
(THF, 20 C, several hours), suitability for various
ligands with electron-acceptor, as well as bulky elec-
tron-donor substituents on phosphorus, makes us to
prefer procedure c.
amines, such as butyl- and isobutylamine, occur in
preference for reduction of the former to give butyl-
benzene [3]. Furthermore, bulkier substituents on phos-
phorus (o-tolyl instead of phenyl) favor not only in-
creased conversion, but also increased selectivity of
the reaction (i.e. ArNHR/ArH ratio) [3]. The effect of
steric properties of bidentate ligands on the catalytic
activity and selectivity of complexes in amine aryla-
tion reactions have been discussed in [5 7]. On the
one hand, as shown in [7], prerequisite for successful
oxidative addition stage is complete dissociation of
one diphosphine ligand, what is favored by complexes
with sterically congested ligands. On the other side,
there is some evidence to show that increased steric
bulk of ligand much accelerates -hydride reduction
of aryl halide [5]. Hamann and Harwig [3] reported on
the predominance of the first factor in their studied
reaction, but these data can not be evidently extended
to other systems.
Complexes IIa IIg are amorphous white or light
orange solid substances (IId is claret). When heated
above 200 C, they decompose without melting with
liberation of palladium black, but they are resistant to
atmospheric oxygen and can be handled in air. Com-
plexes IIa IIc, IIf, and IIg are readily soluble in
chloroform and methylene chloride, IId in butanol,
and IIe in acetone.
As model we chose coupling reactions of two aryl
bromides strongly differing in reactivity, electron-
acceptor 4-bromoacetophenone and electron-donor
N,N-dimethyl-4-bromoaniline. The first was reacted
with aniline, isobutylamine, and morpholine [reaction
(3)] and the second, with aniline and isobutylamine
[reaction (4)] in the presence of 0.5 and 5 mol % of
catalysts II, respectively, and sodium tert-butylate as
base.
The catalytic activity of complexes II was inves-
tigated in amine arylation reactions which are widely
explored both from theoretical and from practical
viewpoints. Our special interest has been attracted by
the fact that palladium complexes of known ligand
IIa are rather effective catalysts in arylation of sub-
stituted anilines with aryl bromides [4 6], whereas
coupling of 4-bromobutylbenzene with aliphatic
0.5 mol% II, 85 C
NR1R2
(3)
+ R1R2NH
CH3CO
Br
CH3CO
PhMe, t-BuONa
IIIa IIIc
IVa IVc
III, IV, R1 = H, R2 + Ph (a), i-Bu (b); R1 + R2 = CH2CH2OCH2CH2 (c).
5 mol% II, 90 C
Me2N
NHR
(4)
+ RNH2
Br
Me2N
PhMe, t-BuONa
IIIa, IIIb
Va, Vb
III, V = R = Ph (a), i-Bu (b).
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EFFECT OF STERIC AND ELECTRONIC PROPERTIES OF PALLADIUM COMPLEXES
209
The results of reaction (3) are listed in Table 1. In
the reaction with aniline, all complexes II prepared
by us proved to be more active catalysts than known
complex IIa, complexes IIb, IIf, and IIg being the
most active. The latter three, while in another order,
are the most active in the cross coupling with mor-
pholine. To discuss the resulting data, let as consider
the catalytic cycle of the reactions (3) and (4),
presented in the scheme.
Table 2. Results of cross coupling of N,N-dimethyl-4-
bromoaniline with amines IIIa and IIIb in the presence of
5% mol of catalysts IIa IIg at 90 C [reaction (4)]
Yield of reaction products, % (GLC)
Comp. no.
Va after 12 ha
Vb after 24 h
IIa
IIb
IIc
IId
IIe
IIf
1.5 (60.5)a
10.0
5.9
10.0
8.8b
5.8b
P
P
Cl
Pd
Pd
P
P
12.4
Cl
0c
P
P
29.5 (61.5)
16.0
7.3
6.1
IIg
P
P
P
P
ArNR1R2
ArX
a
Parenthesized are the yields after 24 h in the presence of
Pd
P
b
P
10% mol of catalyst. Palladium black precipitates almost
c
immediately after beginning of heating.
precipitates after 30-min heating.
Palladium black
arylation of all the three amines with 4-bromoaceto-
phenone we can conclude that the rate of reaction (3)
is controlled by steric properties of the amines, rather
than nucleophilic, since the rate-limiting stage of the
reaction is nucleophilic attack on the palladium atom
in the strongly congested intermediate B (or A).
P
Ar
Ar
X
P
P
Pd
P
Pd
R1R2N
A
According to [3, 4], aryl bromides with strong elec-
tron-donor substituents are scarcely prone to coupling
with amines. Hence, the substrate conversion in reac-
tion (4) with aniline in the presence of 5% mol of the
complex Pd(dba)2/10% Ia after 12 h at 90 C was as
low as 26% [3]. Upon prolonged heating of the reac-
tion mixture at 90 C the yield of the product increased
to 60% and did not grow further. We obtained
analogous results in reaction (4) with complexes II
(Table 2).
P
P
Ar
X
Pd
t-BuOH,
NaX
R1R2NH
P
B
Ar
X
Pd
P
R1R2NH
t-BuONa
On the assumption that intermediate A formed by
oxidative addition of aryl halide undergoes partial
dissociation of one the phosphine centers to give co-
ordinately unsaturated complex B that is attacked by
amine in the transmetalation stage, such dissociation
should be more facile in an intermediate containing
electron-acceptor or bulky substituents on phosphorus.
Probably, it is the optimal combination between the
electron-donor and steric properties of the substituents
make complexes IIf and IIg more active in reaction
(3), whereas the di-tert-butylphosphino group in com-
plex IId is too strong donor, and the diisopropylphos-
phino group in complex IIc is insufficiently bulky.
The lower catalytic activity of complexes IIc and IId
is especially noticeable in the reactions with morpho-
line and isobutylamine, though with the latter com-
pound that is the least reactive among all the three
amines the results are leveled. Analyzing the results of
Hence, in reaction (4) with compound IIe, per-
fluorinated analog of complex IIa, palladium preci-
pitates almost immediately. Evidently, here, the elec-
tron-acceptor effect of the perfluorophenyl radicals
renders phosphorus a weak donor and, as a result, the
reduction potential of Pd(0) is low, and palladium
black precipitates before oxidative addition of the
weakly electrophilic N,N-dimethyl-4-bromoaniline.
Note that complex IId rather successfully catalyzed
the reaction with the electrophilic 4-bromoacetophe-
none, i.e. the oxidative addition stage of reaction (3)
had enough time to occur here. This fact provides
indirect evidence to show that transmetalation is ac-
tually the rate-limiting stage of reaction (3). With
other complexes II, a strong dependence of substrate
conversion on catalyst quantity was revealed for reac-
tion (4) (Table 2, complexes IIa and IIf). Therewith,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 2 2005

210
VEITS, MUTSENEK
the yields with both complexes almost leveled at
10 mol% of catalyst, on account of deactivation of the
latter under prolonged heating. The results of reaction
(4) with isobutylamine seem to be of low preparative
value. It is just to be mentioned here that we found
among the reaction products no reduction product,
N,N-dimethylaniline, whose fraction was rather large
with other bidentate diphosphine complexes [3].
(CDCl3), , ppm: 1.12 2.30 m (28H), 6.60 7.15 m
(8H). 31P NMR spectrum (CH2Cl2), P, ppm: 41.10
(28%), 41.80 (28%), 49.0 (44%). Found, %: C 49.13;
H 6.07. C24H36Cl2OP2Pd. Calculated, %: C 49.71;
H 6.21.
Synthesis of complexes IIb IId from bis(benzo-
nitrile)palladium dichloride and ligands Ib and Id.
b. [2,2 -Bis(dicyclohexylphosphino)diphenyl oxide]-
palladium dichloride (IIb). Ligand Ib and 0.87 mg
of bis(benzonitrile)palladium dichloride were mixed
with 5 ml of THF and placed into a round-bottom flask.
The reaction mixture was stirred for 1 h at 20 C, left
overnight, and the solvent was removed in a vacuum.
A dark orange oily residue was dissolved in a
minimum of methylene chloride or benzene (ca. 1 ml)
and the reaction product was precipitated with 5 ml of
hexane. The precipitate was filtered off, washed with
ether (3 2 ml), and dried in a vacuum to give 150 mg
(90%) of complex IIb. Compound IId was obtained
analogously.
Complex IId.Yield 95%. 1H NMR spectrum
(CDCl3) ppm: 1.23 1.42 m (36H), 6.65 7.23 m (8H).
31P NMR spectrum (n-BuOH), P, ppm: 51.56 (14%),
52.67 (14%), 59.17 (72%). Found, %: C 52.26; H
6.72. C28H44Cl2OP2Pd. Calculated, %: C 52.88, H
6.92.
Hence, if in the catalytic arylation of amines with
highly electrophilic and fast reacting aryl halides we
could reveal certain regularities in the effect of the
electron-donor and steric characteristics of catalysts
II, no analogous conclusions could be made from the
results obtained in this work with passive aryl halides,
such as N,N-dimethyl-4-bromoaniline. Further inves-
tigations with a wider range of aromatic substrates
strongly differing in electrophilicity are necessary.
EXPERIMENTAL
1
The H and 31P NMR spectra were obtained on a
Varian VXR-400 spectrometer against internal TMS
and external 85% phosphoric acid, respectively. All
manipulations were carried out under dry argon. Sol-
vents were dried by standard procedures. Chromato-
graphic studies were performed on a Tsvet-500 gas
chromatograph.
Synthesis of complexes IIe IIg from dibenzo-
nitrilepalladium dichloride and crude ligands Id
Ig. c. [2,2 -Bis(dipentafluorophenylphosphino)di-
phenyl oxide]palladium dichloride (IIe). Crude li-
gand Id, 828 mg, the dark brown oil obtained
by treatment of the reaction mixture from the prepara-
tion of ligand Id with 10 ml of degassed distilled
water and 10 ml of methylene dichloride, drying of
the organic phase over calcined magnesium sulfate
and prolonged exposure it to a vacuum (1 mm Hg) at
40 50 C for removal of the solvents and traces of
tetramethylethylenediamine, was placed in a round-
bottom flask filled with argon. Bis(benzonitrile)palla-
dium dichloride, 223 mg, in 10 ml of THF was then
added with stirring. Precipitate formation began
almost immediately. The reaction mixture was stirred
for 4 h at 60 C (1 h with complexes IIf and IIg) and
left overnight. The solvents were then removed in a
vacuum to leave a dark claret oil that was dissolved
in 3 ml of methylene chloride or benzene. The solu-
tion was treated with 10 ml of hexane to precipitate
the reaction product. The precipitate was washed with
ether and dried in a vacuum to give 418 mg (66%) of
Synthesis of complexes IIa IIc from palladium
chloride and ligands Ia Ic. a. [2,2 -Bis(diphenyl-
phosphino)diphenyl oxide]palladium dichloride
(IIa). A mixture of ligand Ia, 285 mg, and 5 ml of
absolute ethanol was placed in a round-bottom flask
filled with argon. Palladium chloride, 88.7 mg, was
dissolved in a minimun of dilute HCl (0.5 ml of conc.
HCl in 150 ml of water), and the resulting solution
was slowly added with stirring to the ligand solution.
The reaction mixture was stirred for 3 h at 60 C (with
complexes IIb and IIc, for 2 h at 20 C) and left over-
night. Yellow crystals formed and were filtered off,
washed successively with 3 ml of water, ethanol, and
ether, and dried in a vacuum (in most cases, crude
product can be used without purification that includes
its precipitation with hexane from methylene chloride
or benzene) to give 304 mg (85%) of complex IIa.
31P NMR spectrum (CH2Cl2):
18.75 ppm. Pub-
lished data [8]: P(CHCl3) 19.3 pPpm. Complexes IIb
and IIc were prepared analogously.
Complex IIb. Yield 90%. 1H NMR spectrum
(CDCl3), , ppm: 0.96 2.03 m (44H), 7.04 7.56 m
(8H). 31P NMR spectrum (CH2Cl2), P, ppm: 20.10
(50%) and 31.32 (50%). Found, %: C 57.86; H 6.95.
C36H52Cl2OP2Pd. Calculated, %: C 58.43; H 7.03.
complex IId. 31P NMR spectrum (C6H6):
19.31
ppm. Found, %: C 40.69; H 1.12. C36H8Cl2F2P0OP2Pd.
Calculated, %: C 40.17; H 0.74.
Complex IIc. Yield 87%. 1H NMR spectrum
Complexes IIf and IIg were obtained analogously.
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EFFECT OF STERIC AND ELECTRONIC PROPERTIES OF PALLADIUM COMPLEXES
211
Complex IIf. Yield 78%. 1H NMR spectrum
(acetone-d6), , ppm: 1.10 1.60 m (32H), 6.60
6.98 m (8H). 31P NMR spectrum (CHCl3), P, ppm:
36.69 (20%), 38.85 (60%), 45.71 (20%). Found, %:
C 50.89; H 6.47. C26H40Cl2OP2Pd. Calculated, %:
C 51.37; H 6.59.
Complex IIg. Yield 77%. 1H NMR spectrum
(CDCl3), , ppm: 1.10 1.25 m (18H), 6.50 7.24 m
(18H). 31P NMR spectrum (CHCl3), P, ppm: 39.46
(28%), 39.76 (28%), 40.25 (44%). Found, %: C 56.47;
H 5.13. C32H36Cl2OP2Pd. Calculated, %: C 56.86;
H 5.33.
graphy on silica gel, elution with 1:10 ethyl acetate
hexane or 1:5 diethyl ether hexane. The final pro-
ducts were light brown oils.
4-Anilinoacetophenone (IVa). Yield 78%. 1H
NMR spectrum (CDCl3) , ppm: 2.17 s (3H), 6.25
br.s (1H), 7.0 d (2H), 7.08 t (1H), 7.17 d (2H), 7.34 t
(2H), 7.86 d (2H).
4-(Isobutylamino)acetophenone (IVb). Yield
1
62%. H NMR spectrum (CDCl3), , ppm: 1.0 d (6H),
1.53 m (2H), 1.34 m (1H), 2.22 s (3H), 4.33 br.s (1H),
7.35 d (2H), 7.62 d (2H).
1
4-Morpholinoacetophenone (IVc). Yield 84%. H
Cross coupling of p-bromoacetophenone with
amines in the presence of catalysts IIa IIg [reac-
tion (3)]. p-Bromoacetophenone, 0.7 g, and aniline,
0.39 g, were dissolved in 42 ml of toluene. The
ampule was filled with argon and acharged with
0.003 mmol of catalyst II, 57.6 mg of dry sodium
tert-butylate, and 6 ml of the prepared toluene solu-
tion. The ampule was then sealed and thermostated at
85 C for 1 or 2 h. A precipitate quickly dropped from
the transparent dark orange reaction mixture. The
ampule was cooled, 3 ml of solution was taken, fil-
tered through a bed of silica gel to remove the catalyst
and sodium bromide. The products were eluted with
ethanol, the composition of the filtrate was controlled
by TLC (elution with 1:3 diethyl ether hexane). The
sample was evaporated in a vacuum, the oily residue
was dissolved in 2 ml of toluene, 36 l of ethylben-
zene was added, and the mixture was analyzed by
GLC (injector temperature 250 C, detector tempera-
ture 250 C, oven temperature 60 220 C, heating rate
5 /min, helium flow rate 30 ml/min). The resulting
data are listed in Table 1.
NMR spectrum (CDCl3), , ppm: 2.20 s (3H), 3.04
br.t (4H), 3.83 br,t (4H), 7.35 d (2H), 7.62 d (2H).
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